M1629 Polaprezinc As a Potent Inducer of Anti-Oxidative Stress Enzyme, Heme Oxygenase 1

Abstract

G A A b st ra ct s animals that received tap water for 11 days (controls). Rats were observed daily for fluid intake, weight changes, bowel movements, loose stools and rectal bleeding. Samples of distal ileum, and proximal and distal colon were collected for (1) the analysis of myeloperoxidase (MPO) activity, an index of neutrophil infiltration, (2) the histological evaluation of mucosal damage, and (3) the determination of the expression of the proinflammatory cytokine, TNFalpha and MOR mRNA by real time qRT-PCR. Results: Histological analysis showed no surface epithelium lesions in the ileum and colon from control animals as well as in the ileum of treated animals, whereas there were erosions of the epithelium, ulcerations and edema in the distal colon of treated rats. MPO activity was similar in the ileum of control (5.07±0.74 U/mg tissue) and treated group (5.75±0.61 U/mg), whereas it was increased in the proximal colon (11.16±1.67 U/mg vs. controls 4.13±0.55 U/mg) and markedly increased in the distal colon vs. controls (21.96±3.8 U/mg vs. 3.09±0.35 U/mg, p<0.003). There was a 3-fold increase of TNF-alpha mRNA levels in the distal colon in the DSS treated animal (4.47±0.71) compare to the controls (1.42±0.24; p<0.017). By contrast, there was a decrease in the expression of MOR mRNA in the distal colon in DSS treated animals (0.97±0.22) compared to controls (2.0±0.44), whereas the levels of MOR mRNA in the ileum of DSStreated (1.14±0.29), which did not develop detectable inflammation, were comparable to the levels observed in control animals (1.26±0.3). Conclusions: These data show an inverse relationship between the level of inflammation and the expression of MOR mRNA. The lower levels of MOR mRNA in inflamed tissue compared to controls might be due to receptor down regulation induced by increased release of opioids induced by inflammation.